Plasmids are extrachromosomal, autonomously replicating genetic elements which are used extensively as vehicles for cloning foreign DNA and the study of replication control. The main objective of the proposed research will be the development of a mathematical model for the replication control of R1 plasmids. The model will be based on the sequence of molecular events which are thought to initiate a round of plasmid replication. The model will integrate many facets of replication control into one complete model. The model will be tested for its ability to accurately simulate the replication process and to predict the current available experimental observation. The model will then be used to test the plausibility of various hypotheses concerning the biochemical mechanisms involved in the regulation of plasmid copy number, and/or to suggest the conditions under which a hypothesis is plausible. The model for plasmid will be included into a well structured mathematical model of a single-cell of Esherichia coli. Such an inclusion will allow the a priori predictions of copy number for a variety of growth conditions and for various mutations in the regulatory elements. The model also can be used to explore the host-plasmid interactions and the effects of various subcellular mechanisms on the overall system response - a response that can be quantitatively measured. Experiments are required either for estimation of model parameters or for verification of model predictions. Experiments will be performed to obtain information on the growth rate dependence of the concentration of the regulatory components.